Improvement of myelopoiesis in cyclophosphamide-immunosuppressed mice by oral administration of viable or non-viable Lactobacillus rhamnosus

JULIO VILLENA; ANDRES GRAMAJO LOPEZ; SUSANA SALVA; SUSANA ALVAREZ

Mar del Plata, Argentina

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

Sociedad Argentina de Inmunología

Recent research shows that gut microbiota is able to control immunity in distant tissues through regulation of hematopoiesis at primary immune sites as bone marrow (BM). We demonstrated that the dietary supplementation with probiotic lactic acid bacteria (LAB) improves steady-state and emergency granulopoiesis, the respiratory innate immune response and the resistance against respiratory pathogens in immunosupressed hosts. While the viability of the LAB is an important factor to achieve optimal protective effects, it is possible to stimulate immunity using non-viable LAB. The aim of this work was to evaluate whether viable or non-viable immunobiotic Lactobacillus rhamnosus CRL1505 (LrV or LrNV) was able to reduce alterations induced by cyclophosphamide (Cy) on BM hematopoietic stem cells (HSCs), myeloid and erythroid multipotent precursors (MMP and EMP), through the balance between apoptosis and cellular proliferation. Adult Swiss-mice were orally treated with LrV or LrNV (108 cells/d/mouse) during 5 consecutive days. On day 6, lactobacilli-treated and untreated control mice received one intraperitoneally dose of Cy (150 mg/kg). Cy decreased HSCs (Lin-Sca-1+c-Kit+), MMP (Gr-1+Ly6G+Ly6C-) and EMP (Terr117+), triggered cell apoptosis at 12h and decreased cell proliferation in BM. Lactobacilli treatments were able to significantly promote early recovery of HSCs and MMP. Both LrV and LrNV treatments did not prevent damage by apoptosis of these populations. However, the preventive oral administration of L. rhamnosus was able to increase the proliferative capacity of BM cells measured by BrdU incorporation. These findings reveal that L. rhamnosus CRL1505 is able to accelerate the recovery of Cy-induced immunosuppression. For the first time we demonstrate that a LAB directs innate immune cell development via promoting myelopoiesis. Non-viable L. rhamnosus could be a good and safe resource for reducing chemotherapy-induced immunosuppression in cancer patients.